Hematopoietic stem and progenitor cell (HSPC) transplantation is a proven therapy for the treatment of certain malignant and nonmalignant hematologic diseases and metabolic disorders. Sources of HSPC for transplantation include bone marrow, mobilized peripheral blood, and umbilical cord blood (UCB) (Goldman and Horowitz, 2002; Fruehauf and Seggawiss, 2003: Broxmeyer, et al., 2006). Physicians routinely perform transplants of bone marrow, mobilized peripheral blood stem cells and umbilical cord blood. These procedures require that sufficient numbers of hematopoietic stem and progenitor cells be harvested from healthy normal donors, or from patients before they develop a given condition or while they are in remission. The harvested materials are subsequently administered to patients whose hematopoietic system and presumably its diseased or malformed tissues and cells have been eradicated. After transplantation, the transplanted stem cells travel to or “home” to the appropriate bone marrow microenvironment niches, lodge within such niches, proliferate and produce new stem cells, a process called self-renewal (Porecha, et al., 2006; Broxmeyer, 2006; Hall et al., 2006). The cells also differentiate into lineage restricted progenitor cells and mature cells, thus restoring the blood forming hematopoietic system necessary for the health of the recipient. Progenitor cells are usually present in the transplanted materials and may be required in these grafts in order to produce mature cells. However, since progenitor cells are not stem cells and cannot self-renew, they participate in transplant therapy for only a limited period of time.
Because the transplant procedure stresses the transplanted material, a successful transplant requires that sufficient cells be transplanted to account for cells killed or damaged during the procedure. This presents a large problem for the transplant of umbilical cord blood grafts as these grafts include very limited numbers of stem cells. For this reason, cord blood grafts usually cannot be used to successfully transplant adults. Similarly 10-25% of patients and normal donors fail to mobilize sufficient cells for use in transplant procedures. In some patient populations, particularly those treated with some chemotherapeutic agents, failure to mobilize is seen in upward of 50% of patients. In general, the more cells that can be transplanted the greater the likelihood that the transplant will be successful, for example, current best practices recommend that peripheral blood stem cell transplantation procedures typically require minimum administration of approximately 2 million CD34+ cells per kilogram of recipient patient body weight, the more CD34+ cells that can be acquired and subsequently transplanted, the better the patient outcome (Pulsipher, 2009).
Inadequate stem cell number, inability to migrate/home to appropriate marrow niches, or poor engrafting efficiency and self-renewal of hematopoietic stem and progenitor cells can adversely affect transplant outcome, measured by the multi-step process of repopulation. Numerous approaches have been tried to try and expand the number of human hematopoietic stem and progenitor cells within isolated grafts in ex vivo settings with limited success. Strategies to improve HSPC transplantation efficacy is needed to overcome the challenge faced by the medical profession. Some aspects and embodiments of the invention disclosed herein address this need.